[unreadable] Several diseases, such as myelomeningocele, cancer, trauma, infection, and inflammation, may adversely affect the bladder, and many patients must ultimately undergo bladder replacement. However, current bladder replacement techniques involve the use of intestinal segments, which are associated with significant perioperative morbidity and long-term complications. As an alternative to the use of intestine, we plan to utilize the fields of tissue engineering and stem cell biology to develop novel biological bladder substitutes that restore and maintain normal function, while also providing insight on the developmental mechanisms of the bladder. For patients in whom suitable donor tissue does not exist, such as with bladder cancer or bladder agenesis, multipotent stem cells are envisioned as a potentially endless and viable source of cells from which the desired tissue can be derived. The broad objective of this proposal is to combine the principles of stem cell biology and tissue engineering for bladder regenerative applications. This is a novel approach to tissue engineering of the bladder that is expected to yield morphologically accurate and functional tissue for bladder replacement. Combining tissue engineering techniques with this potentially endless source of versatile cells could lead to bladder replacement without the morbidity and complications of current therapies. Ultimately, I intend to combine technologies from both the tissue engineering and stem cell biology fields to optimize the scalability of the bladder inductive process in vitro so that it can be adapted to in vivo models for bladder replacement. [unreadable] [unreadable]